Manufacture of condensation products



Patented Jan. 28, 1941 UNITED STATES MANUFACTURE OF CONDENSATIONPRODUCTS Gerhardt Haberland, Breslau, Germany, assign-or to WinthropChemical Company, Inc., New York, N. Y., a corporation of New York NoDrawing. ApplicationMay 6, 1939, Serial No. 272,149. In Germany May 10,1933 Claims.

This invention relates to a process of manufacturing condensationproducts.

Alpha-halogen fatty acid esters may be reacted with carbonyl compoundsof the aliphatic, aromatic-aliphatic and hydroaromatic series in thepresence of certain metals such as magnesium and zinc with the formationof beta-hydroxy carboxylic acid esters. This reaction is known under thename Reformatzkys reaction.

In accordance with the present invention it is most surprising that alsobeta-halogen fatty acid esters may be reacted with carbonyl compounds ofthe kind above specified. In this case the corresponding gamma-hydroxycarboxylic acid esters, their derivatives respectively are formed;adipinic acid esters are formed only as a byproduct by the interactionof 2 molecules of the beta-halogen fatty acid ester with one another.Preferably the chlorine and bromine compounds are used as thebeta-halogen fatty acid esters, but in many cases also the iodinecompounds may be used. The alcohol radical of the ester group isoptional. The new process is particularly suitable for introducing apropionicacid chain into hydrogenated polycyclic systems, containing acarbonyl group. Most surprising is the relatively high reactivity oftricyclic ketones in which the two ortho-positions to the carbonyl groupare substituted. The reaction products which are obtainable from thetricyclic ketones may be condensed to tetracyclic ketones.

The invention is illustrated by the following examples without beingrestricted thereto:

Ezrample 1 5 grams of G-methoxy-tetralone-1 are heated with 5.5 grams ofbeta-bromopropionic: acid ethylester in benzene in the presence of 0.7gram of magnesium powder. After the addition of a 40 slight quantity ofiodine reaction takes place while the mixture becomes turbid. After 3hours the mixture is cooled, then decomposed by means of ice-water anddilute sulfuric acid and thereafter extracted with ether. The ether isdistilled 45 off from the ethereal solution and the residue saponifiedby means of a methylalcoholic potassium hydroxide solution with theaddition of Water. After extracting the neutral components from thereaction mixture by means of ether, the

50 mixture is acidified by means of dilute hydrochloric acid, the6methoxy-tetralol-l-propionic acid precipitated is dissolved in etherand after the removal of the ether the residue is distilled in a highvacuum. The product distils while si- 55 multaneously splitting offwater at 0.3 mm. pressure from l85-190 C. in the form of a colorless oilwhich soon crystallizes. After recrystallization from methanol andbenzine 1.5-2 grams of colorless crystals are obtained which melt at117.5-l18 C. The product is probably the 6-methoxy-dihydronaphthalene-l-propionic' acid.

Example 2 Example 3 7.5 grams of l-keto-2-methy1-'l-methoxy-1,2,3,4-tetrahydrophenanthrene are treated with 6 grams ofbeta-bromo-propionic acid ethyl ester in benzene in the presence of 0.8gram of mag- 20 nesium powder. After 10 hours heating the reactionmixture is decomposed by means of ice and dilute hydrochloric acid andthen extracted with ether. The ether is distilled off from the etherealsolution and the residue is boiled with 2 alcoholic potassium hydroxidesolution. The unchanged parts of the initial ketone are then extractedfrom the mixture by means of ether. By acidification of the dilutealkaline solution the lactone of the 1-hydroxy-2-methyl-7-methoxy- 3012,3,4-tetrahydrophenanthrene-l-propionic acid is precipitated; byrecrystallization from dilute methanol or acetone colorless crystals.melting at 194 C. may be obtained. The reaction product may be subjectedto further condensation as described in my copending application forLetters Patent Ser. No. 221,013 filed July 23, 1938, now Patent No.2,193,674. Also in this case a tetracyclic ketone is obtained whichafter splitting off of the methyl group from the methoxy group 40 showsa very high oestrus activity in the small dose of a few gamma.

I claim:

1. The process of manufacturing condensation products which comprisesreacting upon a carbonyl compound selected from carbonyl compounds ofthe aromatic-aliphatic and hydroaromatic series with a beta-halogenpropionic acid ester in the presence of a metal of the group consistingof magnesium and zinc.

2. The process of manufacturing condensation products which comprisesreacting upon a carbonyl compound selected from carbonyl compounds ofthe aromatic-aliphatic and hydroaromatic series with a beta-halogenpropionic acid ester in the presence of a metal of the group consistingof magnesium and zinc and in the presence of a solvent which is inert tothe reacting components.

3. Process as claimed in claim 2 in which a polyhydronaphthalene-ketoneis used as the carbonyl compound.

4. Process as claimed in claim 2 in which a polyhydrophenanthrene-ketoneis used as the carbonyl compound.

5. The process of manufacturing condensation products which comprisesreacting upon l-keto- 2-methy1-7-methoxy-1,2,3,4 tetrahydrophenanthrenewith a beta-bromopropionic acid ester in benzene in the presence ofmagnesium.

GERI-IARDT HABERLAND.

